Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2H-benzimidazol-2-one derivatives


Journal of Biomolecular Structure and Dynamics, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1080/07391102.2023.2262601
  • Journal Name: Journal of Biomolecular Structure and Dynamics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core
  • Keywords: Antiproliferative activity, benzimidazole, docking, MD simulation
  • Süleyman Demirel University Affiliated: Yes


Cancer is a global public health problem that affects millions each year. Novel anticancer drug candidates are in need to treat various cancers and to overcome the resistance that exists against drugs in use. Benzimidazole derivatives have been reported as anticancer agents. These lead us to synthesize similar benzimidazole derivatives and investigate their anticancer activity. In this study, six new 1,3-dihydro-2H-benzimidazol-2-one-based molecules (2a-f) were synthesized. The structures of these molecules were verified by spectroscopic methods. The antiproliferative activities of molecules 2a-f were screened against a panel of human cancer cell lines, including the liver, colon, lung, and breast. The molecules were also tested towards normal human lung cell line to determine their selectivity. The results demonstrated that compound 2d had the highest cytotoxic effect compared to compounds 2a-c, 2e, and 2f against DLD-1 and MDA-MB-231 cell lines. The binding potential of the relatively active compound, 2d, with three targets was investigated through molecular docking. The stability of target-compound complexes procured from the docking was explored through molecular dynamics (MD) simulation. The docking and MD simulation studies revealed that compound 2d had the highest potential to bind to GALR3 among the targets. Furthermore, the computational pharmacokinetic study demonstrated that the synthesized compounds had drug-like properties. Communicated by Ramaswamy H. Sarma.